This proposal requests continued support for a Program Project Grant (PPG) to conduct epidemiologic and biostatistical research on iatrogenic causes of cancer by investigators at the Kenneth Norris Jr. (University of Southern California) Comprehensive Cancer Center. This PPG is currently in its 16th year of continuous funding. The professional staff of this Program consists of 11 epidemiologists and statisticians with major research interests in iatrogenic exposures and cancer. The Scientific Program of the current application consists of 3 case-control studies. The successful conduct of these 3 projects depends on 5 core resources. The 4 projects include the following: (1) A continuation of an ongoing case-control study of the relationship of hormone replacement therapy and breast cancer risk in postmenopausal women. An expanded study will allow more detailed and precise evaluation of duration and latency effects, the evaluation of interactions and adequate adjustment for confounding factors; (2) A continuation of an ongoing case- control study of analgesics and diuretics and renal cell carcinoma. Preliminary results suggest that acetaminophen is associated with a greater increment in risk than aspirin, but the strong correlation between different formulations requires larger sample sizes to determine independent effects; and A continuation of an ongoing case-control study of diagnostic radiation and acute myelogenous leukemia. Preliminary data suggest a dose response relationship between trunk x-rays and risk but results are not statistically significant. The major core resource for this PPG is the Cancer Surveillance Program, a rapid ascertainment population-based tumor registry. Other core resources include a Medical Record Retrieval Core for validating self-reported prescription medications, diagnostic and therapeutic radiation, a Control Identification Core for identifying neighborhood controls for case-control studies, a Statistical Core for developing strategies for analyzing the types of studies described above and an Administrative Core for overseeing the scientific direction of the PPG and handling its fiscal administration.